title: Application of high-throughput sequencing for studying genomic variations in congenital heart disease.
abstract: Congenital heart diseases (CHD) represent the most common birth defect in human. The majority of cases are caused by a combination of complex genetic alterations and environmental influences. In the past, many disease-causing mutations have been identified; however, there is still a large proportion of cardiac malformations with unknown precise origin. High-throughput sequencing technologies established during the last years offer novel opportunities to further study the genetic background underlying the disease. In this review, we provide a roadmap for designing and analyzing high-throughput sequencing studies focused on CHD, but also with general applicability to other complex diseases. The three main next-generation sequencing (NGS) platforms including their particular advantages and disadvantages are presented. To identify potentially disease-related genomic variations and genes, different filtering steps and gene prioritization strategies are discussed. In addition, available control datasets based on NGS are summarized. Finally, we provide an overview of current studies already using NGS technologies and showing that these techniques will help to further unravel the complex genetics underlying CHD.
authors.affiliation: Department of Cardiovascular Genetics, Experimental and Clinical Research Center (ECRC), Charité-University Medicine Berlin and Max Delbrück Center (MDC) for Molecular Medicine, Lindenberger Weg 80, 13125 Berlin, Germany. Department of Biochemistry, Free University Berlin, Berlin, Germany. Tel.: +49-(0)30-450540123; Fax: +49-(0)30-84131699; silke.sperling@charite.de.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Dorn
authors.forename: Marcel
authors.initials: M
authors.lastname: Grunert
authors.forename: Silke R
authors.initials: SR
authors.lastname: Sperling
mesh_terms: D030541:Databases, Genetic; D056726:Genetic Association Studies; D014644:Genetic Variation; D023281:Genomics / Q000379:methods*; D006330:Heart Defects, Congenital / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans
keywords: congenital heart disease; genomics; next-generation sequencing; sequence variations; variation filtering; whole-exome datasets